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A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
Hyperlipidemia: Management with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors
Muhammed Shahreyar1, Salem A Salem1, Mannu Nayyar1
1From Division of Cardiology, Department of Medicine, University of Tennessee Health Sciences Center, Memphis, TN (MS, SAS, MN, NG, SKGK); Division of Nephrology, Department of Medicine, University of Tennessee Health Sciences Center, Memphis (LKG); Department of Physician Assistant Studies, University of Tennessee Health Sciences Center, Memphis (LKG); Regional One Health, Memphis (SKGK).
Abstract:
Coronary artery disease is the leading cause of death in United States. Hyperlipidemia is an independent and potentially reversible risk factor for coronary artery disease. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, collectively known as statins, have been the mainstay of pharmacologic therapy. Their availability, ease of administration, low cost, and strong evidence behind safety and efficacy makes them one of the most widely prescribed lipid-lowering agents. However, some patients may be intolerant to statins, and few others suffer from very high serum levels of cholesterol in which statin therapy alone or in combination with other cholesterol-lowering agents is insufficient in reducing serum lipid levels to achieve desired levels. In 2015, the Food and Drug Administration approved a new family of lipid-lowering agents, collectively known as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.PCSK9 inhibitors are biologically active molecules that decrease serum low-density lipoprotein cholesterol compared with statin therapy alone. They serve as an alternative to statins for patients who are intolerant to statin or as supplemental therapy in those patients for whom lower levels in serum low-density lipoprotein cholesterol are not achieved by statins alone. This article discusses PCSK9 inhibitors, their mechanism of action, indications, efficacy, safety, costs and limitations.
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